Dr. Jonas Salk founded the Salk Institute for Biological Studies to solve vital questions in biology and medicine through interdisciplinary research. This strategy is still evident, as the Salk Institute brings biologists, chemists and physicists together to tackle the most pressing questions of our time. Excellent science has always relied on advances in instrumentation. In this application, the Salk Institute requests funds to obtain a liquid chromatography-mass spectrometry (LC-MS) system for lipidomics. Specifically, a ThermoScientific Vanquish UHPLC and Q Exactive (QE) hybrid quadrupole-Orbitrap mass spectrometer would be purchased. The Institute will house the LC-MS system in the Vincent J. Coates Mass Spectrometry Center where it will be accessible to all major and minor users listed in this proposal. A QE was selected because of its superior performance over comparable instruments, and compatibility of this mass spectrometer with ThermoScientific's LipidSearch Software. LipidSearch automatically quantifies and identifies lipids from lipidomics datasets, solving the primary bottleneck in modern lipidomics research. The power of this system will be demonstrated through preliminary data obtained using this instrument in collaboration with Thermo. Lipidomics is emerging as a powerful approach in biological and biomedical research. The Salk Institute recruited Professor Alan Saghatelian, a lipidomics expert, to its faculty last year; however, the Institute currently lacks an available mass spectrometer for lipidomics experiments. The requested UHPLC-QE system has several advantages (e.g., >140K resolution, and <3 ppm accurate mass) over comparable instruments at most cores, including facilities at nearby institutions (UCSD and The Scripps Research Institute). These advantages have led to interest from scientists at the Salk Institute, neighboring institutions, UT Southwestern Medical Center in Dallas, and Beth Israel Medical Deaconess Center in Boston. These researchers comprise the major and minor users in this application, who plan to use the acquired LC-MS to study problems in cancer, regenerative medicine, and metabolic and neurodegenerative diseases. The Salk Institute has the necessary administrative and management plans in place to support this LC-MS for years, and is committed to the long- term care of this instrument. This UHPLC-QE system will lead to new discoveries in biomedically significant fields, and train the next generation of scientists in usin the power of mass spectrometry for biological research. In doing so, the proposed LC-MS system will further the original vision of the Salk by integrating research fields (analytical chemistry and biology) to investigate human disease.